Acquired fibrosing diseases in humans have several common features. Tissue fibrosis is preceded by injury to and/or inflammation of the normal tissue. Infiltrations of the tissue by T cells and monocytes are present in the early phases of fibrosis development.
Systemic sclerosis (SSc, scleroderma) is a prototypic systemic fibrosing disease associated with increased accumulation of collagen type I, III, IV, VI, VII, XVI, XVIII. Cellular and/or humoral immunity to types I, III and IV have been described in patients with SSc. The disease most characteristically involves the skin which becomes thick and tightly bound to underlying structures. The internal organs commonly involved are gastrointestinal tract, lungs, kidneys, and heart.
T lymphocytes via synthesis of cytokines of different types can modulate the functions of fibroblasts and monocytes/macrophages as well as a variety of other target cells. With regards to fibrosis, the production of fibrogenic cytokines by T cells such as IL-4, TGF-β1 and β2, can directly stimulate synthesis of collagen by fibroblasts in culture. T cells by secreting interferon (IFN) gamma can activate macrophages, which in turn can synthesize several fibrogenic cytokines including platelet derived growth factor, TGF-β1 and β2 which in turn can stimulate fibroblasts to increase synthesis of collagen.